Daiichi Sankyo and ArQule acknowledged today that ArQule’s lead product, the hepatocellular carcinoma (HCC) candidate tivantinib (ARQ 197), has failed the Phase III METIV-HCC trial.
Tivantinib did not meet its primary endpoint in METIC-HCC of improving overall survival, the companies said. Their statement did not include details of the results, saying those would be presented at an unspecified “upcoming scientific forum.”
METIV-HCC—which stands for MET-high patients receiving tivantinib in advanced HCC—is a biomarker-selected, double-blind, placebo-controlled, randomized Phase III trial comparing tivantinib (2:1) to best supportive care in patients with MET-overexpressing, inoperable HCC intolerant to, or previously treated with, systemic therapy.
A total of 340 patients with MET-overexpressing HCC analyzed by a validated immunohistochemical assay were randomized in the trial’s intent-to-treat population. Beyond overall survival, the trial measures several secondary endpoints, including progression-free survival and safety.
Tivantinib is an oral inhibitor of the MET receptor tyrosine kinase that has been under development for second-line treatment of patients with MET-overexpressing HCC. Tivantinib has been granted Orphan Drug Designation by the FDA for the treatment of HCC.
ArQule has developed tivantinib through a licensing, co-development, and co-commercialization agreement with Daiichi Sankyo covering the U.S., Europe, South America, and the rest of the world, excluding Japan, China (including Hong Kong), South Korea, and Taiwan. In those four countries, Kyowa Hakko Kirin is ArQule’s co-development partner.
“Despite the negative outcome of this study, we remain committed to applying rigorous science to unmet needs for patients with cancer,” Antoine Yver, M.D., M.Sc., evp and global head, oncology research and development, Daiichi Sankyo, said in a statement.
Tivantinib is one of three Phase III candidates in Daiichi Sankyo’s cancer pipeline. The other two are quizartinib, an oral FLT3-internal tandem duplication (ITD) inhibitor, for newly diagnosed and relapsed/refractory FLT3-ITD+ acute myeloid leukemia, and pexidartinib, an oral colony-stimulating factor 1 receptor (CSF-1R) inhibitor, for tenosynovial giant cell tumor, also known as pigmented villonodular synovitis, and giant cell tumor of the tendon sheath.
Daiichi Sankyo said last year its cancer pipeline had more than 20 small molecules and monoclonal antibodies with novel targets in both solid and hematological cancers.